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Free Radicals and Neuroprotection in Traumatic Brain and Spinal Cord Injury

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Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

This chapter reviews the considerable body of evidence that supports the role of reactive oxygen species (ROS), reactive nitrogen species (RNS) and their derived oxygen free radicals in the pathophysiology of acute traumatic brain injury (TBI) and spinal cord injury (SCI). Free radical‐induced oxidative damage to membrane lipids and proteins occurs in the injured brain of spinal cord within the first minutes and hours and has been implicated in the disruption of neuronal ion homeostasis, exacerbation of glutamate‐mediated excitotoxicity, mitochondrial respiratory dysfunction and microvascular structural and functional damage. Lipid peroxidation (LP) is a key mechanism of the radical‐induced secondary injury. Several free radical scavengers and LP inhibitors have been shown to be neuroprotective in animals models of TBI and/or SCI strongly implicating free radical‐induced LP as an important target for inhibition of secondary CNS injury. The glucocorticoid steroid methylprednisolone which has been shown to decrease post‐traumatic LP in the injured spinal cord when administered in large doses has been shown to improve neurological recovery in SCI clinical trials. The non‐glucocorticoid 21‐aminosteroid tirilazad has also shown evidence of efficacy in SCI patients and in a subset of TBI patients who have post‐traumatic subarachnoid hemorrhage. Improved antioxidants approaches are presented which either more potently inhibit LP or that scavenge the RNS peroxynitrite (PN) or its highly reactive free radical products. Finally, the feasibility of developing compounds with dual antioxidant mechanisms is discussed.

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Abbreviations

LP:

lipid peroxidation

RNS:

reactive nitrogen species

ROS:

reactive oxygen species

SCI:

spinal cord injury

TBI:

Traumatic brain injury

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Authors
  1. E. D. Hall
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 10962, 140 Old Orangeburg Road, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Department of Neurosciences Division of Neurology, Medical University of South Carolina, 29425, 96 Jonathan Lucas Street, Suite 309, Charleston, SC, USA

    Naren Banik

  3. Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, 29209, 6439 Garners Ferry Road Building 2, Room C11, Columbia, SC, USA

    Swapan K. Ray

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Hall, E.D. (2009). Free Radicals and Neuroprotection in Traumatic Brain and Spinal Cord Injury. In: Lajtha, A., Banik, N., Ray, S.K. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30375-8_10

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